The rLVS ΔcapB/iglABC vaccine provides potent protection in Fischer rats against inhalational tularemia caused by various virulent Francisella tularensis strains.

The rLVS ΔcapB/iglABC vaccine provides potent protection in Fischer rats against inhalational tularemia caused by various virulent Francisella tularensis strains.
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DOI:
10.1080/21645515.2023.2277083
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发表时间:
2023-12-15
影响因子:
4.8
通讯作者:
Bozue, Joel A.
Bozue, Joel A.
中科院分区:
医学3区
文献类型:
--
作者:
Mlynek, Kevin D.;Cline, Curtis R.;Biryukov, Sergei S.;Toothman, Ronald G.;Bachert, Beth A.;Klimko, Christopher P.;Shoe, Jennifer L.;Hunter, Melissa;Hedrick, Zander M.;Dankmeyer, Jennifer L.;Mou, Sherry;Fetterer, David P.;Qiu, Ju;Lee, Eric D.;Cote, Christopher K.;Jia, Qingmei;Horwitz, Marcus A.;Bozue, Joel A.

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Francisella tularensis是需要使用许可疫苗的几种生物治疗剂之一,以确保在一系列病毒f。有希望的Tularemia疫苗候选者是RLVSΔCAPB/IGLABC(RLVS),其中载体是capb基因中有缺失的LVS菌株,并另外表达包含蛋白质IGLA,IGLB和IGLC的蛋白质的融合蛋白。菌株SCHU S4(FRAN244),A型菌株(FRAN255)或tick式A型A型菌株(FRAN254),并监测所有RLV疫苗包括107个CFU RLV的单一剂量为A型A型菌株提供了100%的保护,所有未接种的大鼠都屈服于所有F. tularensis菌株的气溶胶挑战。 F. tularensis菌株。
Francisella tularensis is one of the several biothreat agents for which a licensed vaccine is needed. To ensure vaccine protection is achieved across a range of virulent F. tularensis strains, we assembled and characterized a panel of F. tularensis isolates to be utilized as challenge strains. A promising tularemia vaccine candidate is rLVS ΔcapB/iglABC (rLVS), in which the vector is the LVS strain with a deletion in the capB gene and which additionally expresses a fusion protein comprising immunodominant epitopes of proteins IglA, IglB, and IglC. Fischer rats were immunized subcutaneously 1–3 times at 3-week intervals with rLVS at various doses. The rats were exposed to a high dose of aerosolized Type A strain Schu S4 (FRAN244), a Type B strain (FRAN255), or a tick derived Type A strain (FRAN254) and monitored for survival. All rLVS vaccination regimens including a single dose of 107 CFU rLVS provided 100% protection against both Type A strains. Against the Type B strain, two doses of 107 CFU rLVS provided 100% protection, and a single dose of 107 CFU provided 87.5% protection. In contrast, all unvaccinated rats succumbed to aerosol challenge with all of the F. tularensis strains. A robust Th1-biased antibody response was induced in all vaccinated rats against all F. tularensis strains. These results demonstrate that rLVS ΔcapB/iglABC provides potent protection against inhalational challenge with either Type A or Type B F. tularensis strains and should be considered for further analysis as a future tularemia vaccine.
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发表时间: 1995-12-27
期刊: TRANSPLANTATION
影响因子: 6.2
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